Recently, we have seen many parents asking about pediatric hematuria. The common feature is that they do not understand the causes of hematuria and the diseases involved, so we are publishing this article to provide a way to understand hematuria.
Diagnostic thinking about pediatric hematuria
Hematuria is the most common symptom of urinary tract disorders in children. Foreign statistics show that the incidence of asymptomatic hematuria among school-age children is 0.4-4.1%. In 1986, the results of urine screening of 224291 healthy children aged 2-14 years in 21 provinces and cities by the renal group of the Chinese Academy of Pediatrics in China showed that the incidence of asymptomatic hematuria was 0.42%, while in 1996, the renal group of the Chinese Academy of Pediatrics collected renal biopsy data of 2315 children in 20 units, and 341 cases of simple hematuria accounted for 14.7%. It can be seen that hematuria has a high incidence in children in China. Liu Xiaoying, Department of Traditional Chinese Medicine and Pediatrics, Hubei Provincial Hospital of Traditional Chinese Medicine
There are many causes of hematuria, including various renal parenchymal disorders, urinary tract infections, stones, tumors, malformations, trauma, drugs, and systemic bleeding disorders. Its etiology is complex and difficult to diagnose, especially in children with isolated hematuria without proteinuria, edema and hypertension, and it is often not easy to clarify the etiology. Therefore, it is very important to conduct selective and planned investigations in children with hematuria in order to clarify the cause, determine the prognosis and formulate follow-up and treatment plans as early as possible. The diagnosis of hematuria can be made according to the following steps.
1.Classification of hematuria
(1) According to the number of red blood cells in the urine – microscopic hematuria and carnal hematuria
Those with increased red blood cells found under the microscope are called microscopic hematuria. Commonly used criteria.
(1) Centrifugal urine erythrocytes ≥ 3 / high magnification field.
② Urine sediment red blood cell count > 8×106/L.
The naked eye can see that the urine is “meat wash” color or blood-like is called “naked eye hematuria”. Generally, when urine red blood cells > 2.5×109/L (1000mL of urine containing 0.5mL of blood) can be seen in sarcoid hematuria.
(2) According to the presence or absence of symptoms – symptomatic hematuria and asymptomatic hematuria
Symptomatic hematuria refers to children with some urological symptoms such as edema and hypertension in addition to hematuria, or hematuria is one of the clinical manifestations of systemic diseases such as bleeding disorders, systemic infections and coagulation disorders. Asymptomatic hematuria means that the child does not have any other symptoms except hematuria. It is also called simple hematuria (renamed as isolated hematuria in 2001).
(3) According to the source of red blood cells in urine – glomerular hematuria and non-glomerular hematuria
Birch and Fairly first reported in 1979 to distinguish the source of hematuria according to urine morphology, which facilitates clinical diagnosis.
Glomerular hematuria: refers to hematuria of glomerular origin.
(i) Primary glomerular diseases: such as acute or/and chronic glomerulonephritis, nephrotic syndrome, acute progressive nephritis, IgA nephropathy, hereditary nephritis, etc.
(ii) secondary glomerular diseases: such as systemic lupus erythematosus nephritis, purpura nephritis, hepatitis B-associated nephritis, hemolytic uremic syndrome, pulmonary hemorrhagic nephritis syndrome, etc.
(iii) Simple hematuria (isolated hematuria).
Non-glomerular hematuria: hematuria originates from the urinary system below the glomerulus.
①Acute and chronic infections of the urinary tract.
② renal pelvis, bladder, ureteral stones and idiopathic hypercalciuria.
③ Idiopathic renal hemorrhage (left renal vein compression syndrome or nutcracker phenomenon);
④ congenital renal and vascular malformations such as polycystic kidney, bladder diverticulum, arteriovenous fistula, hemangioma, etc.
⑤ tumors, trauma and foreign bodies.
(6) drug-induced renal and bladder injury such as cyclophosphamide, sulfonamides, aminoglycoside antibiotics such as gentamicin, etc.
(7) Infections such as tuberculosis, protozoa and spirochetes.
Bleeding caused by systemic diseases: such as thrombocytopenic purpura, natural bleeding in newborns, hemophilia, etc.
2.Diagnostic steps of hematuria
(1) Determine whether it is true hematuria
The diagnosis of hematuria should first exclude the following conditions that can produce pseudohematuria.
(1) Ingestion of food (such as honey) or drugs (such as rhubarb, rifampin, phenytoin sodium) containing large amounts of artificial color (such as aniline) can cause red urine.
② hemoglobinuria or myoglobinuria.
(iii) porphyrituria.
④ uric acid salts in the urine of newborn infants can make the diapers red.
⑤ Blood stool or menstrual blood contamination.
True hematuria is defined as taking 10mL of clean fresh middle urine (morning urine is good), centrifuging (1500 rpm) for 5min, and taking the sediment for microscopic examination, when the red blood cells ≥ 3 / high magnification field, and appear more than 3 times to have pathological significance. At present, the commonly used urine analyzer (test paper method) to detect urinary occult blood can not be used as a basis for the diagnosis of hematuria, but only as a screening test.
(2) Determining the site of bleeding
After the determination of hematuria, the source of hematuria should be determined first, and then the primary cause can be identified.
The morphological examination of urine sediment red blood cells is a commonly used test at present. If abnormal red blood cells are predominant (>60%), glomerular hematuria is indicated. If the morphology of red blood cells is basically normal and homogeneous is the main reason for non-glomerular hematuria, the hematuria originates from the renal pelvis, calyces, ureter, bladder or urethra, which is mostly seen in urinary tract infection, stone, tuberculosis, tumor and trauma. Factors affecting the morphology of urine red blood cells include: age, urine specific gravity, urine pH, application of diuretics, urinary tract infection, and episodes of carnal hematuria.
② Urine sediment examination sees red blood cell tubular pattern and renal tubular epithelial cells, indicating that hematuria is renal parenchymal. If the urine protein quantification is >500mg/24h in microscopic hematuria, or >990mg/24h or >660mg/L in sarcoid hematuria, it mostly indicates glomerular disease.
③Means volume of red blood cells in urine: The mean volume of red blood cells in urine (MCV) and distribution curve are measured by automatic hematocrit analyzer, if MCV＜72fl and small cell distribution, it means that hematuria originates from glomerulus, the sensitivity of this method is 95%, the specificity is 96%, and the subjective error of the detector can be overcome.
④Urine erythrocyte electrophoresis: The rate of movement of urinary erythrocytes within a certain distance was observed to be (20.64±1.72) s for glomerular and (27.27±1.66) s for non-glomerular.
(⑤) Urinary immunoglobulin particles in the tube: If a tube containing a large amount of IgG1TH protein can be found in the urine, it is mostly renal parenchymal hemorrhage, mainly glomerulonephritis, and partly interstitial nephritis.
3.Analysis of the correlation between hematuria and diseases
(1) Glomerular hematuria
Hematuria with edema, hypertension, tubular and proteinuria found in urine or systemic symptoms should be considered as primary or secondary glomerular diseases:.
(i) hematuria after a recent skin infection or pharyngitis, glomerulonephritis after acute streptococcal infection should be considered first.
(ii) With bleeding spots, anemia, jaundice, and renal insufficiency should be considered hematuria syndrome.
(iii) With edema and massive proteinuria should be considered nephrotic syndrome.
④ with skin purpura, purpura nephritis should be considered.
(⑤ with rash, anemia and fever should be considered lupus nephritis.
(6) history of unexplained fever, wasting, anemia and hemoptysis should be considered pulmonary hemorrhagic nephritis syndrome.
(7) Fever with flushing of face, neck and upper chest, hypotension, shock and oliguria after the fever subsides should be considered as epidemic hemorrhagic fever.
(8) Hereditary nephritis (Alport syndrome) should be considered when accompanied by deafness, anemia, and progressive deterioration of renal function, especially in boys.
The following diseases should be considered when hematuria is the main manifestation.
(1) Recovery from glomerular disease: A small amount of microscopic hematuria may remain in the recovery period of acute nephritis, acute nephritis and allergic purpura nephritis that persists. Therefore, it is important to follow up the symptoms and signs in the acute phase. Most of these diseases can be clearly diagnosed after taking medical history.
②IgA nephropathy: Most children with this disease present with recurrent hematuria, and about 20% present with nephrotic syndrome. The prognosis is good for those who present with hematuria, which usually starts at school age. The kidney biopsy is commonly characterized by thylakoid hyperplasia on light microscopy, with varying degrees of IgA deposition on immunofluorescence, as well as complement C3 and small amounts of other immunoglobulins. Diagnosis is dependent on renal biopsy.
(iii) Thin basement membrane disease: also known as familial recurrent hematuria. The clinical presentation is persistent microscopic hematuria. Sarcopenic hematuria often occurs after a respiratory infection. The main basis for diagnosis is the presence of patients with hematuria of the same nature in the family; the presence of one of the two parents with hematuria is extremely helpful. The glomerular lesion in this disease is a thinning of the basement membrane (<250 nm, and electron microscopy after renal biopsy can provide the diagnosis.
④Hereditary nephritis: early stages may be seen only as simple hematuria, especially in girls, with mild clinical symptoms. However, the course of the disease is progressive, with neurological deafness and ophthalmopathy. The differential diagnosis is often not difficult when combined with family history.
⑤ Simple hematuria (isolated hematuria):Children with persistent microscopic hematuria and intermittent sarcoid glomerulonephritis can be clinically diagnosed as simple hematuria after hereditary nephritis and familial recurrent hematuria are excluded.
There are two clinical presentations.
Recurrent botryoidal hematuria: normal urine routine examination or microscopic hematuria between episodes, with triggers of hematuria episodes such as respiratory infections and strenuous physical activity.
Persistent microscopic hematuria: most of them are detected during physical examination or routine urine tests due to other diseases, and the urine protein does not exceed 1g/24h.
Types of glomerular lesions on renal biopsy are: normal, slightly altered, and thylakoid proliferative nephritis (focal, segmental, or diffuse). Immunofluorescence examination may be negative or with immunoglobulin deposition, with IgA nephropathy accounting for 1/3 to 1/2.
(2) Non-glomerular hematuria
Hematuria with urinary frequency, urinary urgency, urinary pain and urinary disorder should be considered as urinary tract infection, renal tuberculosis, hemorrhagic cystitis, foreign body in the bladder or urethra, etc.; hematuria with back pain or abdominal pain should be considered as urinary stones, etc.; hematuria with systemic bleeding symptoms should be considered as systemic coagulation disorder, such as hemophilia, thrombocytopenia and other blood disorders, and occasionally vitamin K or vitamin C deficiency may also complicate hematuria.
If hematuria is not accompanied by systemic or certain systemic symptoms, the following diseases can be considered.
(1) Urological abnormalities: common ones include renal pelvis ureteral junction stenosis, pelvic effusion and polycystic kidney. Large amounts of fluid and infantile polycystic kidneys can sometimes be palpated in the abdomen as a mass. Most of them can be clearly diagnosed by B-type ultrasound and other imaging examinations.
② Hypercalciuria: Idiopathic hypercalciuria can account for 1/5 to 1/3 of asymptomatic hematuria. diagnosis mainly relies on urine calcium measurement: if 24h urine calcium > 0.1 mmol/kg for 2 or more tests, or 2h postprandial urine calcium and creatinine ratio > 0.2 (> 0.8 for infants <6 months; > 0.6 for children 6-12 months =, hypercalciuria can be diagnosed. The diagnosis of idiopathic hypercalciuria must exclude hypercalciuria caused by adrenocorticism, parathyroidism, tubular acidosis, medullary sponge kidney, and corticosteroid administration. Since the incidence of kidney stones in families with idiopathic hypercalciuria can be as high as 30% to 70%, the possibility of hypercalciuria should be considered if there are kidney stones in the family.
Nutcracker phenomenon: The left renal vein travels through the angle between the aorta and the superior mesenteric artery, and if the angle is too narrow, hematuria or proteinuria may occur due to pressure. The diagnosis must be made by B-mode ultrasound or color Doppler vascular ultrasound, and the distal caliber of the left renal vein is more than three times larger than the proximal one, and it is also confirmed that the hematuria comes from one kidney and the urine red blood cells are homogeneous. In boys, it can sometimes be complicated by left spermatic varicocele.
Urologic tumors: The most common type of tumor in children is renal embryonal tumor, but this tumor rarely has hematuria as the first symptom. Urologic tumors are easily detected by imaging.
⑤ Other: rare causes include ruptured renal hemangioma, pelvic vein pelvic fistula and spontaneous (or due to renal puncture) arteriovenous fistula bleeding, where the hematuria comes from one kidney and is quite severe; minor renal contusions and renal arterial and venous embolism can also cause hematuria.
It is difficult to diagnose the above hematuria, and angiography is necessary to clarify the cause; sometimes the cause can only be found when nephrectomy is performed due to severe hematuria that is difficult to stop.
(3) Bidirectional hematuria.
Drug-induced hematuria: The pathogenesis of drug-induced hematuria is nephrotoxic, allergic and mechanical. Hematuria can be symptomatic or asymptomatic, glomerular or non-glomerular.
①Nephrotoxicity: hematuria is caused by damage to the renal tubules and can lead to acute renal failure in severe cases. These drugs include: aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin, etc.), amphotericin B, para-aminosalicylic acid, mercury preparations and gold preparations, etc.
②Allergic: drugs cause interstitial nephritis through immune mechanisms, commonly penicillin, methylpenicillin, benzisoxazole penicillin, ampicillin, pautazone, polymyxin, and sulfonamides. Clinical manifestations include skin rash, abdominal pain or lumbago, scanty urine, increased eosinophilic leukocytes in blood, etc.; hematuria is often accompanied by leukocytes (mostly eosinophilic leukocytes), and there is mostly renal tubular function impairment.
Mechanical: These drugs cause hematuria by forming crystals in the renal tubules and causing mechanical damage to the tubules.
The common ones are sulfonamides and cytotoxic drugs (which produce large amounts of uric acid in the body and form uric acid crystals in the renal tubules), such as 6-mercaptopurine, cyclophosphamide and vincristine; the hyperosmolar diuretics such as mannitol can also cause tubular injury by causing hyperosmolarity in the renal tubules.
In glomerular portal angiopathy, the clinical manifestation is bidirectional persistent microscopic hematuria or intermittent hematuria.
In combination with blood and urine biochemical analysis.
(i) Elevated blood anti-O with decreased complement C3 should be considered post-acute streptococcal infection nephritis.
(ii) With blood hepatitis B surface antigen (+) and/or hepatitis B e antigen (+) and hepatitis B virus antigen deposition in the renal tissue, hepatitis B virus-associated nephritis can be diagnosed.
(iii) Persistent decrease in serum complement, considering primary membranoproliferative nephritis, lupus nephritis, hepatitis B virus-associated nephritis, and chronic glomerulonephritis.
(iv) Positive anti-nuclear antibodies and double helix deoxyribonucleic acid antibodies should be considered lupus nephritis.
⑤ Increased serum immunoglobulin IgA suggests the possibility of IgA nephropathy; IgG, IgM and IgA are all increased, lupus nephritis and chronic nephritis should be considered.
(6) The analysis of urine protein composition is dominated by macromolecular proteinuria, which is mostly seen in acute and chronic glomerulonephritis and nephrotic syndrome; small molecule proteinuria is dominant, suggesting simple nephropathy and interstitial nephritis.
4, combined with renal biopsy analysis.
Kidney biopsy pathological examination has extremely important value for the etiological diagnosis of hematuria, the most common in children are IgA nephropathy, thin basement membrane nephropathy, mild lesional nephropathy and focal segmental glomerulosclerosis; some uncommon glomerular diseases such as Alport syndrome, lipoprotein glomerulopathy, fibronectin glomerulopathy, collagen III glomerulopathy can also be diagnosed, immunopathology for the diagnosis of anti-glomerular basement membrane Glomerulonephritis, IgA nephropathy, IgM nephropathy, lupus nephritis, hepatitis-associated glomerulonephritis, Alport syndrome, and light chain deposition disease are of great value. There is no uniform indication whether to do renal biopsy for isolated hematuria, generally if.
(1) hematuria is aggravated or proteinuria is present.
(2) Decreased renal function, hypertension.
(3) Significant sarcoid hematuria and persistent microscopic hematuria between two episodes of recurrent sarcoid hematuria mostly suggest serious or progressive pathological changes, and renal biopsy should be performed.
5, combined with imaging analysis such as ultrasonography; CT or MRI; intravenous pyelogram; excretory cystourethrography; digital subtraction angiography, etc.